Fragility fractures, which are more prevalent in women, may be significantly influenced by autophagy due to altered bone turnover. As an essential mediator of autophagy, Beclin-1 modulates bone homeostasis by regulating osteoclast and chondrocyte differentiation, however, the alteration in the local bone mechanical environment in female Beclin-1+/− mice remains unclear. In this study, our aim is to investigate the biomechanical behavior of femurs from seven-month-old female wild-type (WT) and Beclin-1+/− mice under peak physiological load, using finite element analysis on micro-CT images. Micro-CT imaging analyses revealed femoral cortical thickening in Beclin-1+/− female mice compared to WT. Three-point bending test demonstrated a 63.94% increase in whole-bone strength and a 61.18% increase in stiffness for female Beclin-1+/− murine femurs, indicating improved biomechanical integrity. After conducting finite element analysis, Beclin-1+/− mice exhibited a 26.99% reduction in von Mises stress and a 31.62% reduction in maximum principal strain in the femoral midshaft, as well as a 36.64% decrease of von Mises stress in the distal femurs, compared to WT mice. Subsequently, the strength-safety factor was determined using an empirical formula, revealing that Beclin-1+/− mice exhibited significantly higher minimum safety factors in both the midshaft and distal regions compared to WT mice. In summary, considering the increased response of bone adaptation to mechanical loading in female Beclin-1+/− mice, our findings indicate that increasing cortical bone thickness significantly improves bone biomechanical behavior by effectively reducing stress and strain within the femoral shaft.

中文翻译：

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通过皮质骨增厚减轻压力可改善成年雌性 Beclin-1+/- 小鼠的骨机械行为

脆性骨折在女性中更为常见，由于骨转换改变，可能会受到自噬的显着影响。作为自噬的重要介质，Beclin-1 通过调节破骨细胞和软骨细胞分化来调节骨稳态，然而，女性 Beclin-1 局部骨机械环境的改变+/-小鼠仍不清楚。在本研究中，我们的目的是研究 7 个月大雌性野生型 (WT) 和 Beclin-1 股骨的生物力学行为+/-对处于峰值生理负荷的小鼠进行显微 CT 图像的有限元分析。显微 CT 成像分析显示 Beclin-1 股骨皮质增厚+/-雌性小鼠与WT相比。三点弯曲测试表明，女性 Beclin-1 的全骨强度增加了 63.94%，刚度增加了 61.18%+/-小鼠股骨，表明生物力学完整性得到改善。经过有限元分析后，Beclin-1+/-与 WT 小鼠相比，小鼠的 von Mises 应力降低了 26.99%，股骨中轴最大主应变降低了 31.62%，股骨远端 von Mises 应力降低了 36.64%。随后，使用经验公式确定了强度安全系数，结果表明 Beclin-1+/-与 WT 小鼠相比，小鼠在中轴和远端区域表现出显着更高的最小安全系数。总之，考虑到女性 Beclin-1 骨骼适应对机械负荷的反应增强+/-在小鼠中，我们的研究结果表明，增加皮质骨厚度可以通过有效减少股骨干内的应力和应变来显着改善骨生物力学行为。